Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Fibroblasts are the most common cell type of the connective tissues found throughout the body and the principal source of the extensive extracellular matrix (ECM) characteristic of these tissues. They are also the central mediators of the pathological fibrotic accumulation of ECM and the cellular proliferation and differentiation that occurs in response to prolonged tissue injury and chronic inflammation. The transformation of the fibroblast cell lineage involves classical developmental signaling programs and includes a surprisingly diverse range of precursor cell types—most notably, myofibroblasts that are the apex of the fibrotic phenotype. Myofibroblasts display exaggerated ECM production; constitutively secrete and are hypersensitive to chemical signals such as cytokines, chemokines, and growth factors; and are endowed with a contractile apparatus allowing them to manipulate the ECM fibers physically to close open wounds. In addition to ECM production, fibroblasts have multiple concomitant biological roles, such as in wound healing, inflammation, and angiogenesis, which are each interwoven with the process of fibrosis. We now recognize many common fibroblast-related features across various physiological and pathological protracted processes. Indeed, a new appreciation has emerged for the role of noncancerous fibroblast interactions with tumors in cancer progression. Although the predominant current clinical treatments of fibrosis involve nonspecific immunosuppressive and anti-proliferative drugs, a variety of potential therapies under investigation specifically target fibroblast biology.

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Fibroblasts in fibrosis: novel roles and mediators

https://archive-ouverte.unige.ch/unige:112949/ATTACHMENT01

EASL Clinical Practice Guidelines on nutrition in chronic liver disease

Nonalcoholic fatty liver disease (NAFLD) affects 25% of the global adult population and is the most common chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH) is the active form of NAFLD, with hepatic necroinflammation and faster fibrosis progression. With an increasing number of patients developing NASH-related end-stage liver disease and pharmacological treatments on the horizon, there is a pressing need to develop NAFLD and NASH biomarkers for prognostication, selection of patients for treatment and monitoring. This requirement is particularly true as liver biopsy utility is limited by its invasive nature, poor patient acceptability and sampling variability. This article reviews current and potential biomarkers for different features of NAFLD, namely, steatosis, necroinflammation and fibrosis. For each biomarker, we evaluate its accuracy, reproducibility, responsiveness, feasibility and limitations. We cover biochemical, imaging and genetic biomarkers and discuss biomarker discovery in the omics era.

Noninvasive biomarkers in NAFLD and NASH - current progress and future promise.

ESPEN guideline on clinical nutrition in liver disease.

Liver cirrhosis affects the results of many of the traditional techniques currently used to evaluate nutritional status. Our aim was to compare the traditional two-compartment model (subjective global assessment and anthropometry and blood tests) of nutritional assessment with a multicompartmental model (body composition analysis) in patients with cirrhosis. Seventy-nine patients and 17 control subjects were studied. Subjective global assessment, anthropometry and blood tests, and body composition analysis were performed for each. The two most important compartments were body cell mass and total body fat. The subjects were classified by each method as well nourished or moderately or severely malnourished. Twenty-five patients (31.6%) were malnourished according to the subjective global assessment, 2 (6.3%) with Child's class A cirrhosis, 10 (34.5%) with class B, and 13 (72.2%) with class C, whereas 24 (30.4%) were malnourished according to the traditional model, 5 (15.6%) in the Child's A group, 8 (27.6%) in B, and 11 (61.1%) in C. According to the multicompartmental model, 48 patients (60.1%) were malnourished, 11 (34.4%) in Child's A, 20 (69%) in B, and 17 (94.4%) in C. The use of the multicompartmental model increased the prevalence of malnutrition by more than 60% in Child's classes A and B patients and by more than 20% in Child's class C patients. Traditional nutritional assessment, although easier, underestimated the prevalence and severity of malnutrition in patients with cirrhosis. The underestimation was more pronounced in Child's class A and B patients.

Comparison of three methods of nutritional assessment in liver cirrhosis: subjective global assessment, traditional nutritional parameters, and body composition analysis.

Hepatic fibrosis in patients with non-alcoholic fatty liver disease is associated with progression of the disease. In the present study, we analyzed the discriminative ability of serum laminin, type IV collagen and hyaluronan levels to predict the presence of fibrosis in these patients. In this preliminary report, we studied 30 overweight patients divided into two groups according to the absence (group I, N = 19) or presence (group II, N = 11) of fibrosis in a liver biopsy. Triglycerides, aspartate aminotransferase, alanine aminotransferase, gamma-glutamyltranspeptidade, hyaluronan (noncompetitive fluoroassay), type IV collagen, and laminin (ELISA) were determined. Group II presented significantly higher mean laminin, hyaluronan, type IV collagen, and aspartate aminotransferase values, which were due to the correlation between these parameters and the stage of fibrosis in the biopsy (Spearman's correlation coefficient, rS = 0.65, 0.62, 0.53, and 0.49, respectively). Analysis of the ROC curve showed that laminin values >282 ng/ml were those with the best diagnostic performance, with 87% accuracy. Association of laminin with type IV collagen showed improvement in the positive predictive value (100%), but with reduction in diagnostic sensitivity (64%). When compared with the criteria of Ratziu et al. for the diagnosis of septal fibrosis, laminin values presented a better diagnostic accuracy (83 vs 70%). Determination of extracellular matrix components in serum, especially of laminin, may identify patients with non-alcoholic fatty liver disease and fibrosis and these components may be used as indicators for liver biopsy in these patients.

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Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease

Background and Aims:  Malnutrition is common in liver cirrhosis patients. However, it is under-diagnosed because liver disease affects the traditional nutritional assessment. An understanding of changes in body composition and the establishment of the tissue-loss pattern in liver cirrhosis patients could help practitioners to better manage malnutrition in this setting. The aims of this study were: to quantify body composition changes, to determine tissue loss pattern, and to assess the relation of these to the severity of hepatic dysfunction.



Methods:  Seventy-nine patients and 17 controls were studied. Total body water and extracellular water were measured using dilution techniques. Intracellular water and body cell mass were calculated from these parameters. Total body fat was obtained using absorptiometry.



Results:  Extracellular water was increased and intracellular water was decreased in patients. The two major compartments (body cell mass and body fat) were significantly reduced, mainly in patients with moderate and severe disease. However, significant losses occurred even in Child–Pugh class A patients. We established a tissue-loss pattern. In Child–Pugh class A patients body fat loss predominated. Child–Pugh class B patients had losses in at least one of the two compartments. Most Child–Pugh class C patients had simultaneous depletion in both compartments.



Conclusions:  Liver cirrhosis was characterized by a significant reduction in body cell mass and body fat and by a redistribution of body water. Significant losses occurred even in patients with mild disease. There was a more pronounced loss of fat in the initial stages, followed by an accelerated loss of body cell mass in the advanced stages of liver cirrhosis.



© 2004 Blackwell Publishing Asia Pty Ltd

Effect of liver cirrhosis on body composition: Evidence of significant depletion even in mild disease

Spontaneous bacterial peritonitis (SBP) is one of the most common and life-threatening complications of cirrhosis. It occurs in 10% to 30% of patients admitted to hospital and recent studies tend to demonstrate that SBP incidence seems to be decreasing in its frequency. A bacterial overgrowth with translocation through the increased permeable small intestinal wall and impaired defense mechanisms is considered to be the main mechanism associated with its occurrence. The Gram-negative aerobic bacteria are the major responsible for SBP episodes and Gram-positive bacteria, mainly Staphylococcus aureus, are being considered an emergent agent causing SBP. The prompt diagnosis of SBP is the key factor for reduction observed in mortality rates in recent years. The clinical diagnosis of SBP is neither sensitive nor specific and the search for new practical and available tools for a rapid diagnosis of SBP is an important endpoint of current studies. Reagent strips were considered a promising and faster way of SBP diagnosis. The prompt use of empirical antibiotics, mostly cefotaxime, improves significantly the short-term prognosis of cirrhotic patients with SBP. The recurrence rate of SBP is high and antibiotic prophylaxis has been recommended in high-risk settings. Unfortunately, the long-term prognosis remains poor.

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Spontaneous bacterial peritonitis: How to deal with this life-threatening cirrhosis complication?

Background and Aim:  Portal hypertensive gastropathy (PHG) is an important cause of bleeding in patients with cirrhosis associated with portal hypertension. Histologically, the condition is characterized by dilation of the mucosal and submucosal vessels of the stomach; however, its mechanisms remain unclear. The aim of the present cross-sectional study was to evaluate the role of portal and systemic hemodynamic features, humoral factors and hepatocellular function in the development and severity of PHG in patients with cirrhosis.



Methods:  Forty-six patients with cirrhosis of different etiologies underwent endoscopy. Portal hypertension was evaluated by hepatic venous pressure gradient (HVPG). The gastric mucosa was analyzed using two diagnostic methods: endoscopy according to the McCormack criteria and histological by histomorphometric analysis.



Results:  The prevalence of PHG according to the endoscopic and histomorphometric methods was 93.4% and 76.1%, respectively. There were no statistically significant differences in HVPG measurements between the patients with mild (16.0 ± 5.9 mmHg) and severe PHG (16.9 ± 6.5 mmHg; P = 0.80) or between patients who did not have (15.2 ± 8.0 mmHg) and those who had PHG (16.3 ± 5.7 mmHg). No correlation was found between the presence or severity of PHG and systemic vascular resistance index (P = 0.53 and 0.34, respectively), Child–Pugh classification (P = 0.73 and 0.78, respectively) or glucagon levels (P = 0.59 and 0.62, respectively).



Conclusions:  The present data show no correlation between the presence or the severity of PHG and portal pressure, Child–Pugh classification or systemic hemodynamics, suggesting that other factors may be involved in the physiopathology of PHG, such as local gastric mucosal factors or other underlying factors.

Mario Kondo

Papers

Comparison of three methods of nutritional assessment in liver cirrhosis: subjective global assessment, traditional nutritional parameters, and body composition analysis.

Serum laminin, type IV collagen and hyaluronan as fibrosis markers in non-alcoholic fatty liver disease

Effect of liver cirrhosis on body composition: Evidence of significant depletion even in mild disease

Spontaneous bacterial peritonitis: How to deal with this life-threatening cirrhosis complication?

Underlying mechanism of portal hypertensive gastropathy in cirrhosis: a hemodynamic and morphological approach.